CSF metabolites associated with biomarkers of Alzheimer's disease pathology.
CSF metabolites associated with biomarkers of Alzheimer's disease pathology.
复制标题
DOI：
10.3389/fnagi.2023.1214932
复制
发表时间：
2023
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
代谢组学技术有助于研究小分子与疾病过程之间的关联。将脑脊液 (CSF) 中的代谢物与阿尔茨海默病 (AD) CSF 生物标志物相关联，可能会阐明与早期 AD 病理学相关的其他变化，并增强我们对该疾病的了解。对来自威斯康星州阿尔茨海默病预防登记处的 161 名个体的非目标代谢物的相对丰度进行了评估。在 269 种 CSF 代谢物和蛋白质生物标志物之间进行了全代谢组关联研究 (MWAS)，这些生物标志物反映了脑淀粉样变性、tau 病理学、神经元和突触变性、星形胶质细胞或小胶质细胞激活和神经炎症。线性混合效应回归分析采用样本相关性的随机截距以及年龄、性别和受教育年限的重复测量和固定效应。代谢组范围内的显着性由 0.05 的错误发现率阈值确定。这些重要的代谢物在当时威斯康星州阿尔茨海默病研究中心的 154 名独立个体中进行了复制。使用脑脊液代谢物全基因组关联研究中的全基因组显着单核苷酸多态性进行孟德尔随机化。全代谢组关联研究结果显示，除 Aβ42/40 和 IL-6 之外的所有生物标志物都有几种显着相关的代谢物。与代谢物和孟德尔随机化分析相关的遗传变异为代谢物与骨髓细胞 2 (sTREM2)、淀粉样蛋白 β (Aβ40)、α-突触核蛋白、总 tau、磷酸化 tau 和神经粒蛋白表达的可溶性触发受体之间的因果关系提供了证据，例如 sTREM2 的棕榈酰鞘磷脂 (d18:1/16:0)，赤藓糖醇用于 Aβ40 和 α-突触核蛋白。这项研究提供的证据表明，脑脊液代谢物与 AD 相关病理学相关，并且其中许多关联可能是因果关系。
Metabolomics technology facilitates studying associations between small molecules and disease processes. Correlating metabolites in cerebrospinal fluid (CSF) with Alzheimer’s disease (AD) CSF biomarkers may elucidate additional changes that are associated with early AD pathology and enhance our knowledge of the disease. The relative abundance of untargeted metabolites was assessed in 161 individuals from the Wisconsin Registry for Alzheimer’s Prevention. A metabolome-wide association study (MWAS) was conducted between 269 CSF metabolites and protein biomarkers reflecting brain amyloidosis, tau pathology, neuronal and synaptic degeneration, and astrocyte or microglial activation and neuroinflammation. Linear mixed-effects regression analyses were performed with random intercepts for sample relatedness and repeated measurements and fixed effects for age, sex, and years of education. The metabolome-wide significance was determined by a false discovery rate threshold of 0.05. The significant metabolites were replicated in 154 independent individuals from then Wisconsin Alzheimer’s Disease Research Center. Mendelian randomization was performed using genome-wide significant single nucleotide polymorphisms from a CSF metabolites genome-wide association study. Metabolome-wide association study results showed several significantly associated metabolites for all the biomarkers except Aβ42/40 and IL-6. Genetic variants associated with metabolites and Mendelian randomization analysis provided evidence for a causal association of metabolites for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), amyloid β (Aβ40), α-synuclein, total tau, phosphorylated tau, and neurogranin, for example, palmitoyl sphingomyelin (d18:1/16:0) for sTREM2, and erythritol for Aβ40 and α-synuclein. This study provides evidence that CSF metabolites are associated with AD-related pathology, and many of these associations may be causal.
登录
查看更多内容
DOI：
10.1083/jcb.200207113
发表时间：
2003-01-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ehehalt R;Keller P;Haass C;Thiele C;Simons K
通讯作者：
Simons K
影响因子：
5.1
作者：
Jiang, Teng;Yu, Jin-Tai;Tan, Lan
通讯作者：
Tan, Lan
影响因子：
5.3
作者：
Hayashi, H;Kimura, N;Yanagisawa, K
通讯作者：
Yanagisawa, K
影响因子：
6.1
作者：
Chao, JC;Swanson, NR
通讯作者：
Swanson, NR
DOI：
10.3233/jad-160195
发表时间：
2017
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Darst BF;Koscik RL;Racine AM;Oh JM;Krause RA;Carlsson CM;Zetterberg H;Blennow K;Christian BT;Bendlin BB;Okonkwo OC;Hogan KJ;Hermann BP;Sager MA;Asthana S;Johnson SC;Engelman CD
通讯作者：
Engelman CD